This proposal seeks continued funding for on-going studies of the application of vibrational optical activity techniques to biologically important molecules. We plan to develop consistent empirical descriptions of the relationship between structure and spectra for several biopolymeric systems. The main thrust will continue to be development of understanding of oligopeptide and polypeptide conformations via VCD (vibrational circular dichroism) and correlation of such data to globular protein VCD. The polypeptide work will focus on determination of characteristic VCD for the beta-sheet and "random-coil" conformations as these do not appear to be unique in our preliminary work. A major effort will be undertaken to factor protein VCD spectra into contributions from component segments of well-defined secondary structure using multi- component analysis methodology. These data will in turn be coupled to existing UV-CD data sets to develop a more complete description of protein secondary structure. Other applications will include structural analysis of membrane proteins and oligopeptides related to drugs. Similar efforts will be continued to develop systematic understanding of polynucleotide, DNA and RNA VCD, environmental effects on nucleic acid conformations and drug-DNA interactions. These latter systems will also compose the focus of an empirically based Raman CID study.